Many patients with type 2 diabetes take oral antidiabetic medications, either as monotherapy or in conjunction with other oral antidiabetic medications or insulin. It’s important you are able to recognize these medications as their use increases the risk of hypoglycemia, especially when taken with insulin. This lesson provides a brief overview of each of the oral antidiabetic medications with a few key things to know about each one. One very important thing to remember about these medications is they are not used for patients with type 1 diabetes. They are only used to treat type 2 diabetes.

Sulfonylureas (ex: glipizide)

Sulfonylureas like glipizide work by binding to potassium channels in the pancreatic beta cells, which leads to more insulin secretion. Because these medications increase insulin secretion, they can induce hypoglycemia. Glipizide is taken thirty minutes before breakfast, so teach your patient to hold the dose if they are not able to eat. The most common side effect of glipizide is photosensitivity, so teach patients to wear protective clothing and sunscreen. They should also avoid drinking alcohol while taking this medication as this can cause a disulfiram-like reaction which involves abdominal cramps, headache, flushing, nausea, and hypoglycemia. 

One key thing to know about glipizide: Increases risk of hypoglycemia when other oral antidiabetics or insulin are used

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Biguanides (ex: metformin)

Metformin works by decreasing hepatic gluconeogenesis and lipogenesis while also increasing the uptake of glucose in muscles. Metformin does not cause hypoglycemia on its own, but hypoglycemia can occur when the medication is taken along with insulin or a sulfonylurea like glipizide. The most troublesome and common side effects of metformin are GI related and include bloating, nausea, vomiting, and diarrhea. The effects can be reduced by taking the medication with meals. A very important thing to remember about metformin is that it is always held for about 48 hours if the patient receives IV contrast because this combination puts the patient at high risk for contrast-induced nephropathy.

One key thing to know about metformin: Avoid use with IV contrast

Thiazolidinediones (ex: pioglitazone/Actos)

Pioglitazone works by increasing insulin sensitivity and the uptake of glucose. Unlike other oral antidiabetic medications, it can be administered without regard to meals. If you have a female patient taking this medication, teach her that it can reduce the effectiveness of oral contraceptives, so other forms of birth control should be utilized. This medication can also cause liver failure and heart failure, so ensure your patient knows what to watch for so they can seek medical care immediately. For liver dysfunction this includes nausea, dark urine, jaundice and abdominal pain. For heart failure this includes edema, rapid weight gain and shortness of breath. 

One key thing to know about pioglitazone: Can be taken without regard to meals

Meglitinides (ex: repaglinide)

Meglitinides like repaglinide work by increasing insulin secretion in pancreatic beta cells. The most common and serious side effect of this medication is hypoglycemia. Note that serum levels of this medication are increased with concurrent use of NSAIDs, hormonal contraceptives, beta blockers and clopidogrel (among many others!), which puts your patient at even higher risk of hypoglycemia. Repaglinide is taken up to 30 minutes before meals in two to three doses per day.

One key thing to know about repaglinide: High risk for hypoglycemia

DPP-4 inhibitors (ex: sitagliptin/Januvia)

Sitagliptin and other DPP-4 inhibitors work by inhibiting an enzyme that leads to increased levels of active incretin hormones, which play a key role in glucose homeostasis. The result is increased insulin release and decrease in glucagon. While hypoglycemia can occur with sitagliptin, it’s more likely to occur if the patient is also taking insulin or a sulfonylurea such as glipizide. Serious adverse reactions include pancreatitis, heart failure and rhabdomyolysis. Teach your patients the signs of these conditions. Signs of pancreatitis include nausea, vomiting and severe abdominal pain. Signs of heart failure are edema, rapid weight gain and shortness of breath. And rhabdomyolysis causes muscle pain, weakness and dark urine.

One key thing to know about sitagliptin: Serious side effects include pancreatitis, heart failure and rhabdomyolysis

Alpha-glucosidase inhibitors (ex: acarbose)

Acarbose works by inhibiting an enzyme in the GI tract which leads to slowed glucose absorption and a reduction in postprandial glucose levels. Acarbose is administered three times per day with the first bite of each meal. Common side effects include flatulence, diarrhea, and abdominal pain. While acarbose does not cause hypoglycemia on its own, hypoglycemia risk is increased when taken along with insulin or a sulfonylurea. A very important thing to know about acarbose is that hypoglycemia must be treated with IV glucose, IM glucagon, or oral glucose (gel, liquid, tablet). Because the medication prevents the breakdown of sucrose, administering jelly, honey or table sugar will not be effective.

One key thing to know about acarbose: If hypoglycemic, give glucose gel

SGLT2 inhibitors (ex: canagliflozin/Invokana and empagliflozin/Jardiance)

Invokana, Jardiance, and other SGLT2 inhibitors work by inhibiting renal tubular sodium-glucose co-transporter 2, which in turn inhibits glucose reabsorption and causes increased excretion of glucose in the urine. Note these medications can cause hypoglycemia on their own and the effects are increased if other antidiabetic medications are taken. In addition, note that patients taking a diuretic or an antihypertensive medication are at higher risk for hypotension while taking an SGLT2 inhibitor. Because of the presence of glucose in the urinary tract, these patients are also at higher risk for UTI, which, in severe cases, can lead to sepsis. Teach patients the signs of UTI which include urinary frequency and pain with urination. And, because this medication can cause increased urination and volume depletion, teach the patient to stay hydrated, to change positions slowly and to report signs of hypotension such as fatigue, dizziness or feeling faint. This medication is taken once each morning with or without food.

One key thing to know about Invokana and Jardiance: High risk for UTI

Dopamine agonist (bromocriptine/Cycloset)

Bromocriptine is an interesting medication because it comes in two formulations. One is used to treat Parkinson’s disease, and the other (Cycloset) is used in type 2 diabetes. It works by increasing insulin sensitivity which reduces fasting and postprandial blood sugar levels. The most common adverse effects are orthostatic hypotension, dizziness, drowsiness and nausea. And, of course, hypoglycemia can occur, especially when taking other antidiabetic medications. Cycloset is taken each morning within two hours of waking and should always be taken with food.

One key thing to know about Cycloset: Assess for hypotension

Review oral antidiabetic medications on the go by tuning in to episode 354 of the Straight A Nursing podcast. Listen from any podcast platform, or straight from the website here.


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References:

Ganesan, K., Rana, M. B. M., & Sultan, S. (2023). Oral Hypoglycemic Medications. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482386/

McIver, L. A., Preuss, C. V., & Tripp, J. (2024). Acarbose. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK493214/

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023a). Acarbose (Precose). In Davis’s Drug Guide (18th ed.). F.A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51003/all/acarbose?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023b). Bromocriptine (Cycloset, Parlodel). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51110/all/bromocriptine?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023c). Canagliflozin (Invokana). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/110121/all/canagliflozin?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023d). Empagliflozin (Jardiance). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/110360/all/empagliflozin?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023e). Glipizide (Glucotrol). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/109049/all/glipiZIDE?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023f). MetFORMIN (Glucophage XR, Glumetza). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51484/all/metFORMIN?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023g). Pioglitazone (Actos). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51614/all/pioglitazone?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023h). Repaglinide (Prandin). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51658/all/repaglinide?refer=true

Vallerand, A. H., Sanoski, C. A., & Quiring, C. (2023i). Sitagliptin (Januvia). In Davis’s Drug Guide (18th ed.). F. A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/109219/all/SITagliptin?refer=true